Wang Ruiying, Yin Junping, Li Jian, Bai Xueli, Liu Hu, Cheng Mengyu, Wang Lei, Chen Yuan, Wei Shuang, Liu Xiansheng
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China.
Heliyon. 2024 Aug 20;10(17):e36337. doi: 10.1016/j.heliyon.2024.e36337. eCollection 2024 Sep 15.
Sivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS.
A retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO), the ratio of PaO to the fraction of inspired oxygen (PaO/FiO), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia.
In the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, < 0.001), more ARDS patients (4.9 % vs. 0.43 %, < 0.001), and more patients with interstitial lung disease (4.9 % vs. 1.49 %, = 0.023), but fewer patients with stroke (17.65 % vs. 19.86 %, < 0.001). Oxygen therapy rates were similar between the groups (79.41 % vs. 80.95 %, = 0.9). The relative risk reduction in 30-day mortality was 88.45 % (95 % confidence interval [CI] 81.23%-93.21 %) for severe/critical COVID-19 patients treated with sivelestat. Sivelestat significantly decreased cytokine levels of interferon alpha (IFNα), interleukin-1 beta (IL-1β), and interleukin-2 (IL-2).In the sivelestat group, the mortality rate was significantly reduced with standard oxygenation and HFNC therapy( < 0.05). The treatment with sivelestat did not increase side effects.
The administration of the neutrophil elastase inhibitor sivelestat may improve clinical outcomes in COVID-19 patients with ALI/ARDS. These findings suggest that sivelestat could be considered an effective treatment option to alleviate pulmonary inflammatory injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
西维来司他是一种中性粒细胞弹性蛋白酶抑制剂，据推测可减轻急诊手术后患者的急性肺损伤。然而，其对2019冠状病毒病（COVID-19）所致急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）患者的疗效仍不确定。本研究旨在评估西维来司他对COVID-19合并ALI/ARDS患者的肺保护作用。
进行一项回顾性研究，纳入2022年10月5日至2023年2月1日期间的2454例COVID-19患者。其中，102例患者接受西维来司他治疗（0.2mg/kg/h），同时确定2352例年龄和性别匹配的对照。采用倾向评分匹配（PSM）分析，将西维来司他组和非西维来司他组按1:1和1:3的比例进行匹配，以进行敏感性分析。主要结局是有效结局的综合指标，包括30天死亡率。次要结局包括动脉血氧分压（PaO）、PaO与吸入氧分数之比（PaO/FiO）的变化以及各种细胞因子水平。安全性评估包括肝功能、肾功能和白细胞减少的评估。
在倾向评分匹配分析中，西维来司他组中重症/危重症患者的比例更高（87.26%对51.02%，<0.001），ARDS患者更多（4.9%对0.43%，<0.001），间质性肺疾病患者更多（4.9%对1.49%，=0.023），但中风患者更少（17.65%对19.86%，<0.001）。两组的氧疗率相似（79.41%对80.95%，=0.9）。接受西维来司他治疗的重症/危重症COVID-19患者30天死亡率的相对风险降低了88.45%（95%置信区间[CI]81.23%-93.21%）。西维来司他显著降低了干扰素α（IFNα）、白细胞介素-1β（IL-1β）和白细胞介素-2（IL-2）的细胞因子水平。在西维来司他组中，标准氧疗和高流量鼻导管氧疗显著降低了死亡率（<0.05）。西维来司他治疗未增加副作用。
给予中性粒细胞弹性蛋白酶抑制剂西维来司他可能改善COVID-19合并ALI/ARDS患者的临床结局。这些发现表明，西维来司他可被视为减轻严重急性呼吸综合征冠状病毒2（SARS-CoV-2）所致肺部炎症损伤的有效治疗选择。
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